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Background:  Vast increases in life expectancy over the last century have led to shifts in population demographics and the emergence of a largely aged population, globally. This has led to a need to understand neurobiological changes associated with healthy aging. Studies on age-related changes in functional connectivity networks have largely been cross-sectional and focused on the default mode network (DMN). The current study investigated longitudinal changes in functional connectivity in multiple resting-state networks over 4 years of aging in cognitively normal older adults.  Methods:  Resting-state functional magnetic resonance imaging scans from older adults ( n  = 16) who maintained "cognitive normal" status over 4 years were retrieved at baseline and follow-up from the Alzheimer's Disease Neuroimaging Initiative database. A seed-based approach was executed in Functional MRI of the Brain Software Library (FSL) to examine significant changes in functional connectivity within the DMN, frontoparietal network (FPN), and salience network (SN) within subjects over time.  Results:  Results indicated significantly ( p  &lt; 0.05, corrected) reduced functional connectivity in the FPN and SN, but not in the DMN at year 4 compared with baseline in older adults who were cognitively stable.  Conclusions:  The current study highlights the importance of a longitudinal approach for understanding changes in functional connectivity. The findings also underscore the need to examine multiple networks within the same participants, given that changes were apparent in the FPN and SN but not in the DMN. Future studies should also examine changes in internetwork connectivity as well as shifts in structural connectivity over time. Impact statement Investigations of age-related changes in functional connectivity have largely been cross-sectional and focused on the default mode network (DMN). The current study examined the DMN as well as the frontoparietal network (FN) and salience network (SN), in a group of healthy aging adults over four years. The results revealed decreased functional connectivity over time, in the FN and SN, but not the DMN. These findings provide insights about the healthy aging brain. They also underscore the need to broaden the scope of functional connectivity analyses beyond the DMN and highlight the use of longitudinal methods.

A Longitudinal Study of Changes in Resting-State Functional Magnetic Resonance Imaging Functional Connectivity Networks During Healthy Aging